Figure 1.

Midbrain dopaminergic neurons are specifically vulnerable in Parkinson's disease. (A) The predominant symptoms of Parkinson's disease (PD) are caused by loss of dopaminergic (DA) neurons in the substantia nigra (SN). According to the dying-back hypothesis, the degeneration of DA neurons is preceded by dysfunction and in turn degeneration of the nigrostriatal pathway, which innervates the caudate nucleus and the putamen that together form the striatum. (B) Compared to healthy controls (left), nigrostriatal degeneration results in the depletion and ultimate loss of the neurotransmitter dopamine on synaptic terminals of striatal neurons (right). (C) The resulting motor symptoms, among others, are usually diagnosed when approximately 30–60% of striatal DA neurons are already lost. However, PD patients can experience non-motors symptoms 20 years before the onset of motor abnormalities in the so-called prodromal phase; these include olfactory dysfunction, sleep disturbances and depression.